THIS PROJECT INVOLVES TWO GOALS: (1) Development of simple tests for detection of chemical abnormalities, suitable for the dried spots of blood already collected from newborn infants to screen for phenylketonuria and other inborn errors of metabolism by methods devised by this laboratory. (2) Search for new inborn errors of metabolism among developmentally disabled subjects whose family history suggests an autosomal recessive mode of inheritance of the disorder. Methods used emphasize use of bacterial inhibition assays, bacterial auxotrophs and special mutants, as well as paper, thin-layer, gas and liquid chromatographic procedure. Recent tests developed include those for arginase deficiency, Lesh-Nyhan Disease and glutathione deficiency. Under development is a test designed to detect any of several inborn errors in the urea cycle, which lead to hyperammonemia. Screening of high-risk individuals has led to detection and study of cases of an apparent variant of aspartylglucosaminuria, and a case of Leigh's disease. Use of high pressure liquid chromatography to detect ultraviolet light-absorbing derivatives of urinary organic acids is under study. Detection and specific diagnosis of various mucapolysaccharidoses by thin-layer and high pressure liquid chromatography is also in progress. BIBLIOGRAPHIC REFERENCES: Garrick, L.M., Dembure, and Garrick, M.D., Interaction between the Synthesis of alpha and beta Globin. Eur. J.Biochem. 58: 339-350, 1975. Naylor, E.W., Genetic Screening and Genetic Counseling: Knowledge, Attitudes and Practices in Two Groups of Family Planning Professionals. Social Biology, 1976, in press.